Trial Outcomes & Findings for Prospective Randomized Evaluation Of Celecoxib Integrated Safety Vs Ibuprofen Or Naproxen (NCT NCT00346216)

Participant milestones
Measure	Celecoxib Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily	Ibuprofen Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily	Naproxen Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Overall Study STARTED	8072	8040	7969
Overall Study COMPLETED	5664	5580	5621
Overall Study NOT COMPLETED	2408	2460	2348

Reasons for withdrawal
Measure	Celecoxib Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily	Ibuprofen Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily	Naproxen Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Overall Study Other	181	231	205
Overall Study No longer willing to participate	600	606	585
Overall Study Withdrawal by Subject	661	692	651
Overall Study Lost to Follow-up	611	588	542
Overall Study Physician Decision	80	76	59
Overall Study Does not meet entrance criteria	13	10	8
Overall Study Death	189	192	228
Overall Study Study terminated by sponsor	11	4	8
Overall Study Missing Subject Summary Status	62	61	62

Baseline characteristics by cohort
Measure	Celecoxib n=8072 Participants Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily	Ibuprofen n=8040 Participants Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily	Naproxen n=7969 Participants Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.	Total n=24081 Participants Total of all reporting groups
Age, Continuous	63.0 Years STANDARD_DEVIATION 9.5 • n=5 Participants	63.2 Years STANDARD_DEVIATION 9.4 • n=7 Participants	63.3 Years STANDARD_DEVIATION 9.4 • n=5 Participants	63.2 Years STANDARD_DEVIATION 9.4 • n=4 Participants
Sex: Female, Male Female	5175 Participants n=5 Participants	5174 Participants n=7 Participants	5096 Participants n=5 Participants	15445 Participants n=4 Participants
Sex: Female, Male Male	2897 Participants n=5 Participants	2866 Participants n=7 Participants	2873 Participants n=5 Participants	8636 Participants n=4 Participants

Outcome measures
Measure	Celecoxib n=8072 Participants Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily	Ibuprofen n=8040 Participants Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily	Naproxen n=7969 Participants Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). ITT (N = 8072, 8040, 7969)	2.3 Percentage of Partcipants	2.7 Percentage of Partcipants	2.5 Percentage of Partcipants
The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). MITT (N = 8030, 7990, 7933)	1.7 Percentage of Partcipants	1.9 Percentage of Partcipants	1.8 Percentage of Partcipants

Outcome measures
Measure	Celecoxib n=8072 Participants Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily	Ibuprofen n=8040 Participants Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily	Naproxen n=7969 Participants Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
The First Occurrence of a Major Adverse Cardiovascular Events (MACE) ITT (N = 8072, 8040, 7969)	4.2 Percentage of Participants	4.8 Percentage of Participants	4.3 Percentage of Participants
The First Occurrence of a Major Adverse Cardiovascular Events (MACE) MITT (N = 8030, 7990, 7933)	3.1 Percentage of Participants	3.6 Percentage of Participants	3.2 Percentage of Participants

Outcome measures
Measure	Celecoxib n=8072 Participants Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily	Ibuprofen n=8040 Participants Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily	Naproxen n=7969 Participants Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) ITT (N = 8072, 8040, 7969)	0.7 Percentage of Participants	0.9 Percentage of Participants	0.7 Percentage of Participants
The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) MITT (N = 8030, 7990, 7933)	0.3 Percentage of Participants	0.7 Percentage of Participants	0.7 Percentage of Participants

Renal and urinary disorders

Renal colic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Renal cyst haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Anaemia

0.19%

15/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.43%

34/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.30%

24/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Anaemia vitamin B12 deficiency

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Aplastic anaemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Coagulopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Haemorrhagic anaemia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Hypochromic anaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Iron deficiency anaemia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Leukocytosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Leukopenia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Lymphadenopathy mediastinal

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Microcytic anaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Pancytopenia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Thrombocytopenia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Blood and lymphatic system disorders

Thrombocytosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Acute coronary syndrome

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Acute left ventricular failure

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Acute myocardial infarction

0.27%

22/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.25%

20/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.23%

18/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Angina pectoris

0.16%

13/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.16%

13/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Angina unstable

0.56%

45/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.51%

41/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.76%

60/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Aortic valve disease

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Aortic valve incompetence

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Aortic valve stenosis

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Arrhythmia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Arrhythmia supraventricular

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Arteriosclerosis coronary artery

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Arteriospasm coronary

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Atrial fibrillation

0.44%

35/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.49%

39/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.45%

36/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Atrial flutter

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Atrioventricular block

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Atrioventricular block complete

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Atrioventricular block second degree

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Atrioventricular dissociation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Bradyarrhythmia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Bradycardia

0.12%

10/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Bundle branch block left

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Bundle branch block right

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac aneurysm

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac arrest

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.11%

9/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac disorder

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac failure

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac failure chronic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac failure congestive

0.39%

31/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.51%

41/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.52%

41/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac tamponade

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac valve disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiac ventricular thrombosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardio-respiratory arrest

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiogenic shock

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiomyopathy

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiopulmonary failure

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiovascular disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Congestive cardiomyopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cor pulmonale chronic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Coronary artery disease

0.52%

42/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.50%

40/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.55%

44/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Coronary artery insufficiency

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Coronary artery occlusion

0.11%

9/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Coronary artery stenosis

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.11%

9/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Coronary artery thrombosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Extrasystoles

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Heart valve incompetence

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Hypertensive cardiomyopathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Hypertensive heart disease

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Ischaemic cardiomyopathy

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Left ventricular dysfunction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Left ventricular failure

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Mitral valve disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Mitral valve incompetence

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Myocardial infarction

0.56%

45/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.88%

70/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.61%

48/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Myocardial ischaemia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Nodal arrhythmia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Palpitations

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Pericardial effusion

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Pericarditis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Pleuropericarditis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Postinfarction angina

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Prinzmetal angina

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Silent myocardial infarction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Sinus bradycardia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Sinus node dysfunction

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Sinus tachycardia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Supraventricular extrasystoles

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Supraventricular tachycardia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Tachyarrhythmia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Tachycardia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Tricuspid valve incompetence

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Ventricular extrasystoles

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Ventricular fibrillation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Ventricular tachycardia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Arteriovenous malformation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Atrial septal defect

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Cardiac septal defect

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Cerebrovascular arteriovenous malformation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Choledochal cyst

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Developmental hip dysplasia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Diverticulitis Meckel's

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Haemorrhagic arteriovenous malformation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Hypertrophic cardiomyopathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Congenital, familial and genetic disorders

Renal hypoplasia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Ear and labyrinth disorders

Deafness

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Ear and labyrinth disorders

Ear discomfort

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Ear and labyrinth disorders

Vertigo

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Ear and labyrinth disorders

Vertigo positional

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Adrenal haemorrhage

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Adrenal insufficiency

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Autoimmune thyroiditis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Goitre

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Hyperparathyroidism

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Hyperparathyroidism primary

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Hyperthyroidism

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Hypogonadism

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Hypoparathyroidism

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Inappropriate antidiuretic hormone secretion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Myxoedema

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Parathyroid disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Endocrine disorders

Thyroid mass

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Cataract

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Diplopia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Eye haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Glaucoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Optic neuropathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Retinal detachment

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Retinal haemorrhage

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Retinal vein occlusion

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Vision blurred

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Visual impairment

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Eye disorders

Vitreous detachment

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Abdominal adhesions

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Abdominal discomfort

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Abdominal hernia

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Abdominal incarcerated hernia

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Abdominal pain

0.17%

14/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.16%

13/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Abdominal pain lower

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Abdominal pain upper

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Abdominal wall haematoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Ascites

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Autoimmune pancreatitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Chronic gastritis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Colitis

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Colitis ischaemic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Colitis ulcerative

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Colonic fistula

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Colonic pseudo-obstruction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Constipation

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Crohn's disease

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Diarrhoea

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Diarrhoea haemorrhagic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Diverticular perforation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Diverticulum

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Diverticulum intestinal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Diverticulum intestinal haemorrhagic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Duodenal ulcer

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Duodenal ulcer haemorrhage

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Duodenal ulcer perforation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Duodenitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Dysphagia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Enteritis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Enterocele

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Enterovesical fistula

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Erosive duodenitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Erosive oesophagitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Faecaloma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Femoral hernia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Food poisoning

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastric perforation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastric ulcer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.15%

12/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastric ulcer haemorrhage

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastric varices

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastric varices haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastric volvulus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastritis

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastritis erosive

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastritis haemorrhagic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastroduodenal haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastroduodenitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastrointestinal haemorrhage

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastrointestinal hypomotility

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastrointestinal necrosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastrointestinal stenosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastrointestinal ulcer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Gastrooesophageal reflux disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Haematochezia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Haemorrhoidal haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Haemorrhoids

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Hernial eventration

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Hiatus hernia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Ileal ulcer

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Ileus

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Ileus paralytic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Incarcerated inguinal hernia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Incarcerated umbilical hernia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Inflammatory bowel disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Inguinal hernia

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Intestinal dilatation

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Intestinal ischaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Intestinal obstruction

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Intestinal perforation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Intestinal ulcer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Intra-abdominal haemorrhage

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Irritable bowel syndrome

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Large intestinal haemorrhage

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Large intestinal obstruction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Large intestinal ulcer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Large intestine perforation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Large intestine polyp

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Localised intraabdominal fluid collection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Lower gastrointestinal haemorrhage

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Megacolon

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Melaena

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Mesenteric artery stenosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Nausea

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Necrotising colitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Neutropenic colitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Obstruction gastric

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Oedematous pancreatitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Oesophageal spasm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Oesophageal stenosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Oesophageal ulcer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Oesophagitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Oesophagitis ulcerative

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Pancreatic cyst

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Pancreatic necrosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Pancreatitis

0.10%

8/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.15%

12/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.15%

12/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Pancreatitis acute

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Pancreatitis chronic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Pancreatitis necrotising

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Peptic ulcer haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Rectal haemorrhage

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Retroperitoneal haematoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Retroperitoneal mass

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Salivary gland calculus

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Small intestinal obstruction

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.11%

9/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Umbilical hernia

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Upper gastrointestinal haemorrhage

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Volvulus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Gastrointestinal disorders

Vomiting

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Adverse drug reaction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Asthenia

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Cardiac death

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Chest discomfort

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Chest pain

0.65%

52/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

1.1%

84/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.92%

73/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Complication associated with device

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Cyst rupture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Death

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Device related thrombosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Drowning

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Drug interaction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Electrocution

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Fatigue

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Feeling hot

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

General physical health deterioration

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Generalised oedema

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Granuloma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Hernia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Ill-defined disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Impaired healing

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Incarcerated hernia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Influenza like illness

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Local swelling

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Malaise

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Multiple organ dysfunction syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Necrosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Non-cardiac chest pain

0.29%

23/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.24%

19/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.29%

23/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Oedema peripheral

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Organ failure

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Pain

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Pelvic mass

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Peripheral swelling

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Polyp

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Pyrexia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Sudden cardiac death

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Sudden death

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Surgical failure

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Systemic inflammatory response syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Vascular stent stenosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

General disorders

Vascular stent thrombosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Acute hepatic failure

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Bile duct obstruction

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Bile duct stone

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Biliary colic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Biliary dyskinesia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Biliary tract disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Cholangitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Cholecystitis

0.10%

8/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Cholecystitis acute

0.11%

9/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Cholecystitis chronic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Cholelithiasis

0.30%

24/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.29%

23/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.15%

12/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Cholestasis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Drug-induced liver injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Gallbladder disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Hepatic cyst

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Hepatic failure

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Hepatic function abnormal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Hepatic lesion

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Hepatic vein thrombosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Hepatitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Hepatitis alcoholic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Jaundice cholestatic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Jaundice hepatocellular

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Liver disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Hepatobiliary disorders

Portal vein thrombosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Immune system disorders

Allergy to arthropod bite

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Immune system disorders

Anaphylactic reaction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Immune system disorders

Anaphylactic shock

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Immune system disorders

Drug hypersensitivity

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Immune system disorders

Hypersensitivity

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Immune system disorders

Sarcoidosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Abdominal abscess

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Abdominal infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Abdominal wall abscess

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Abscess intestinal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Abscess limb

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Abscess neck

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Acute sinusitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Anal abscess

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Appendiceal abscess

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Appendicitis

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Appendicitis perforated

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Arthritis bacterial

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Arthritis infective

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Atypical pneumonia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bacteraemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bacterial diarrhoea

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bacterial disease carrier

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bacterial infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bacterial sepsis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Beta haemolytic streptococcal infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bone tuberculosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Breast abscess

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bronchitis

0.12%

10/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.20%

16/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.21%

17/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bronchitis bacterial

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Bursitis infective

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Campylobacter gastroenteritis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Cellulitis

0.36%

29/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.40%

32/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.40%

32/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Cellulitis of male external genital organ

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Cellulitis staphylococcal

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Cholecystitis infective

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Chronic pulmonary histoplasmosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Chronic sinusitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Clostridium difficile colitis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Clostridium difficile infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Cystitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Cytomegalovirus infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Dengue fever

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Device related infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Diabetic foot infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Diverticulitis

0.15%

12/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.16%

13/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.21%

17/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Embolic pneumonia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Empyema

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Encephalitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Endocarditis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Epididymitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Erysipelas

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Escherichia bacteraemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Escherichia infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Escherichia sepsis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Escherichia urinary tract infection

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Extradural abscess

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Gangrene

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Gastroenteritis

0.15%

12/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.26%

21/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Gastroenteritis bacterial

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Gastroenteritis viral

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Gastrointestinal infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Gastrointestinal viral infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Genitourinary tract infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Groin abscess

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

H1N1 influenza

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

HIV infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Haemophilus infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Helicobacter gastritis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Hepatic infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Herpes oesophagitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Herpes simplex

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Herpes zoster

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Incision site infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Infected skin ulcer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Infectious colitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Infectious pleural effusion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Infective exacerbation of chronic obstructive airways disease

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Infective tenosynovitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Influenza

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Intervertebral discitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Joint abscess

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Kidney infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Klebsiella bacteraemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Klebsiella infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Liver abscess

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Localised infection

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Lower respiratory tract infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Lung infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Lymphangitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Meningitis bacterial

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Meningitis pneumococcal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Necrotising fasciitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Nosocomial infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Ophthalmic herpes zoster

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Oral candidiasis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Orchitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Osteomyelitis

0.11%

9/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Osteomyelitis acute

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Osteomyelitis chronic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Otitis media

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pancreatic abscess

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pancreatitis bacterial

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pancreatitis viral

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Parametritis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Paraspinal abscess

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Parotitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Periodontitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Perirectal abscess

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Peritonitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Peritonitis bacterial

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Peritonsillar abscess

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pharyngitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pharyngitis streptococcal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pleurisy viral

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumococcal sepsis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumonia

0.80%

64/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.99%

79/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.87%

69/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumonia bacterial

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumonia fungal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumonia haemophilus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumonia klebsiella

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumonia pseudomonal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumonia staphylococcal

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pneumonia streptococcal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Post procedural infection

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Postoperative abscess

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Postoperative wound infection

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Prostate infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Proteus infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pulmonary tuberculosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pyelonephritis

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.11%

9/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pyelonephritis acute

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pyelonephritis chronic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pyometra

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Respiratory tract infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Sepsis

0.24%

19/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.25%

20/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.15%

12/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Septic arthritis staphylococcal

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Septic shock

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Sinusitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Skin infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Spinal cord abscess

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Staphylococcal abscess

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Staphylococcal bacteraemia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Staphylococcal infection

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Staphylococcal sepsis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Staphylococcal skin infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Stenotrophomonas infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Subcutaneous abscess

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Tinea pedis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Tonsillitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Tooth abscess

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Tooth infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Tuberculosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Upper respiratory tract infection

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Urinary tract infection

0.20%

16/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.28%

22/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.25%

20/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Urinary tract infection bacterial

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Urosepsis

0.11%

9/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Viral diarrhoea

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Viral infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Viral upper respiratory tract infection

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Vulval abscess

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Wound infection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Wound infection staphylococcal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Accidental exposure to product

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Acetabulum fracture

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Alcohol poisoning

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Anaemia postoperative

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Anastomotic leak

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Animal bite

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Ankle fracture

0.12%

10/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.11%

9/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Arterial injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Arthropod bite

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Back injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Brain contusion

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Burns second degree

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Burns third degree

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Cartilage injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Cervical vertebral fracture

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Chest injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Clavicle fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Compression fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Concussion

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Contusion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Craniocerebral injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Delayed spinal fusion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Extradural haematoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Eye contusion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Face injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Facial bones fracture

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Fall

0.10%

8/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Fat embolism

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Femoral neck fracture

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Neurogenic shock

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Femur fracture

0.14%

11/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.23%

18/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Fibula fracture

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Foetal exposure during pregnancy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Orthostatic hypertension

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Foot fracture

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Forearm fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Foreign body

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Gastrointestinal stoma complication

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Gun shot wound

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Hand fracture

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Head injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Heat exhaustion

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Hepatic rupture

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Hip fracture

0.10%

8/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.20%

16/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Humerus fracture

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Incisional hernia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Intentional overdose

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Intervertebral disc injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Jaw fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Joint dislocation

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Joint injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Laceration

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Ligament injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Ligament rupture

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Limb crushing injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Lower limb fracture

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Meniscus injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Multiple fractures

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Multiple injuries

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Muscle rupture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Nerve injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Overdose

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Patella fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Pelvic fracture

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Periprosthetic fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Perirenal haematoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Post concussion syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Post procedural complication

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Post procedural constipation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Post procedural haemorrhage

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Post procedural oedema

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Post procedural swelling

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Post-traumatic neck syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Postoperative ileus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Postoperative thoracic procedure complication

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Procedural complication

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Procedural pain

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Procedural pneumothorax

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Pubis fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Pulmonary contusion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Radius fracture

0.11%

9/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Respiratory fume inhalation disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Rib fracture

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Road traffic accident

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.11%

9/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Scapula fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Seroma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Skeletal injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Skin abrasion

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Skull fracture

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Spinal column injury

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Spinal compression fracture

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Spinal fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Spinal shock

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Splenic rupture

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Subdural haematoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Subdural haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Tendon rupture

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Thermal burn

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Thoracic vertebral fracture

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Tibia fracture

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Toxicity to various agents

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Traumatic arthritis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Traumatic haemothorax

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Traumatic renal injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Ulna fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Upper limb fracture

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Urinary retention postoperative

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Urostomy complication

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Vascular graft occlusion

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Vascular graft thrombosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Vascular pseudoaneurysm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Wound

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Wound decomposition

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Wound dehiscence

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Wound necrosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Wound secretion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Injury, poisoning and procedural complications

Wrist fracture

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Alanine aminotransferase increased

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Aspartate aminotransferase increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Aspiration bronchial

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Biopsy anus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Biopsy breast

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood bilirubin increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood chromium increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood creatine abnormal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood creatinine increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood glucose abnormal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood glucose increased

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood iron decreased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood pressure increased

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood pressure systolic increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Blood triglycerides increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Clostridium test positive

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Ejection fraction

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Ejection fraction decreased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Electrocardiogram abnormal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Endoscopy gastrointestinal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Fibrin D dimer increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Haemoglobin decreased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Heart rate irregular

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Hepatic enzyme increased

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Liver function test increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Occult blood positive

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Oxygen saturation decreased

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Platelet count decreased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Platelet function test abnormal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Staphylococcus test positive

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Transaminases increased

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Troponin increased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Investigations

Weight decreased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Decreased appetite

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Dehydration

0.12%

10/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.25%

20/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.16%

13/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Diabetes mellitus

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Diabetes mellitus inadequate control

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Diabetic ketoacidosis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Electrolyte imbalance

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Gout

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hypercalcaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hyperglycaemia

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hyperkalaemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hypernatraemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hyperosmolar hyperglycaemic state

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hypocalcaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hypoglycaemia

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hypokalaemia

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.11%

9/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hypomagnesaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hyponatraemia

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hypophosphataemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Hypovolaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Iron deficiency

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Ketoacidosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Lactic acidosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Malnutrition

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Metabolic acidosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Obesity

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Metabolism and nutrition disorders

Type 2 diabetes mellitus

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Arthralgia

0.55%

44/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.41%

33/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.49%

39/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Arthrofibrosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Arthropathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Back pain

0.17%

14/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.21%

17/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.25%

20/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Bone cyst

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Bone disorder

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Bone erosion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Bursitis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Cervical spinal stenosis

0.10%

8/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Chondropathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Compartment syndrome

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Costochondritis

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Exostosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Facet joint syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Felty's syndrome

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Fistula

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Flank pain

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Foot deformity

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Fracture malunion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Gouty arthritis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Intervertebral disc degeneration

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.16%

13/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Intervertebral disc disorder

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Intervertebral disc displacement

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Intervertebral disc protrusion

0.24%

19/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.20%

16/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.20%

16/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Joint ankylosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Joint effusion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Joint instability

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Joint swelling

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Knee deformity

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Kyphosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Lumbar spinal stenosis

0.16%

13/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.19%

15/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.25%

20/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Meniscal degeneration

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Arthritis

0.39%

31/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.41%

33/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.40%

32/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Mobility decreased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Muscle spasms

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Muscular weakness

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Musculoskeletal pain

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Myalgia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Neck pain

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Osteoarthritis

2.5%

201/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

2.6%

206/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

2.4%

189/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Osteoarthropathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Osteolysis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Osteonecrosis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Osteoporosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Pain in extremity

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Pain in jaw

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Pathological fracture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Periarthritis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Polyarthritis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Polymyositis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Pseudarthrosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Rhabdomyolysis

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Rheumatoid arthritis

0.10%

8/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Rotator cuff syndrome

0.12%

10/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Scoliosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Spinal column stenosis

0.16%

13/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.15%

12/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Spinal osteoarthritis

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.20%

16/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Spinal pain

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Spondylitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Spondylolisthesis

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Synovial cyst

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Tendon disorder

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Tendon pain

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Tendonitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Vertebral foraminal stenosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Vertebral osteophyte

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acoustic neuroma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Renal failure

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.26%

21/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.23%

18/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Renal haematoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acute myeloid leukaemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma of colon

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma of the cervix

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma pancreas

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenoma benign

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

B-cell lymphoma

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basal cell carcinoma

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign lung neoplasm

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign neoplasm

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign ovarian tumour

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer recurrent

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder neoplasm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder transitional cell carcinoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bone cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bowen's disease

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Brain neoplasm

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Brain neoplasm malignant

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer

0.25%

20/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer in situ

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer recurrent

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Renal impairment

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer stage I

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer stage IV

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast neoplasm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bronchioloalveolar carcinoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoid tumour

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoid tumour of the duodenum

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoid tumour of the small bowel

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoid tumour of the stomach

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Central nervous system lymphoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cervix carcinoma stage 0

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cholangiocarcinoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Chronic lymphocytic leukaemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Clear cell renal cell carcinoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon adenoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer metastatic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer recurrent

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon cancer stage III

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Colon neoplasm

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Diffuse large B-cell lymphoma stage II

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial adenocarcinoma

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial cancer recurrent

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Endometrial cancer stage III

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Female reproductive neoplasm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Follicle centre lymphoma, follicular grade I, II, III

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Follicular thyroid cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastric neoplasm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal melanoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal stromal cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal stromal tumour

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Gastrointestinal tract adenoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Glioblastoma multiforme

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hairy cell leukaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Head and neck cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hepatic cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hepatic cancer metastatic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Hodgkin's disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intraductal proliferative breast lesion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Invasive ductal breast carcinoma

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Large cell lung cancer stage 0

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Laryngeal squamous cell carcinoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Leiomyoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Leukaemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lip neoplasm malignant stage unspecified

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lipoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lobular breast carcinoma in situ

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung adenocarcinoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung adenocarcinoma stage III

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung cancer metastatic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung carcinoma cell type unspecified stage I

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung carcinoma cell type unspecified stage IV

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung neoplasm malignant

0.17%

14/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.15%

12/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lung squamous cell carcinoma stage II

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lymphocytic leukaemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Lymphoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant mediastinal neoplasm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant melanoma

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant melanoma in situ

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant neoplasm of unknown primary site

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant pleural effusion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Mantle cell lymphoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Meningioma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Mesothelioma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to liver

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic gastric cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic malignant melanoma

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic squamous cell carcinoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myelodysplastic syndrome

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Neoplasm malignant

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-Hodgkin's lymphoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-Hodgkin's lymphoma stage III

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Non-small cell lung cancer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal adenocarcinoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oesophageal carcinoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Oropharyngeal cancer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ovarian cancer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ovarian cancer stage III

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma metastatic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Renal injury

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma stage II

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pancreatic carcinoma stage III

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Papillary cystadenoma lymphomatosum

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Paraproteinaemia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Parathyroid tumour

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Parathyroid tumour benign

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pituitary tumour

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pituitary tumour benign

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Plasma cell myeloma

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer

0.10%

8/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.24%

19/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.25%

20/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Prostate cancer recurrent

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal cancer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cancer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cancer metastatic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal cell carcinoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Renal neoplasm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Small cell lung cancer metastatic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of lung

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Squamous cell carcinoma of skin

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Superficial spreading melanoma stage unspecified

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Sweat gland tumour

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Testis cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Throat cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Thyroid cancer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Transitional cell cancer of the renal pelvis and ureter

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Transitional cell carcinoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Triple negative breast cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Ureteric cancer

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Uterine cancer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Uterine leiomyoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Altered state of consciousness

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Amnesia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Aphasia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Ataxia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Autonomic neuropathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Balance disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Basal ganglia infarction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Basal ganglia stroke

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Brachial plexopathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Brain oedema

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Carotid arteriosclerosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Carotid artery disease

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Carotid artery dissection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Carotid artery occlusion

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Carotid artery stenosis

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Carotid artery thrombosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Carpal tunnel syndrome

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Central nervous system lesion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Central-alveolar hypoventilation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebellar infarction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebral cyst

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebral haematoma

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebral haemorrhage

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebral infarction

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebral ischaemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebrospinal fluid leakage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebrovascular accident

0.49%

39/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.43%

34/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.43%

34/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cerebrovascular disorder

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cervical cord compression

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cervical myelopathy

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cervical radiculopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Chorea

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Cognitive disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Complex regional pain syndrome

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Dementia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Dementia Alzheimer's type

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Depressed level of consciousness

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Diabetic hyperosmolar coma

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Diabetic neuropathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Dizziness

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Dural arteriovenous fistula

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Dysarthria

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Dyskinesia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Embolic stroke

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Encephalomalacia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Encephalopathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Epidural lipomatosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Epilepsy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Facial paralysis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Facial paresis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Generalised tonic-clonic seizure

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Guillain-Barre syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Haemorrhage intracranial

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Haemorrhagic stroke

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Headache

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Hemiparesis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Hydrocephalus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Hypertensive encephalopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Hypoaesthesia

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Hypoxic-ischaemic encephalopathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

IIIrd nerve paralysis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Intracranial aneurysm

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Ischaemic cerebral infarction

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Ischaemic stroke

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Lacunar infarction

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Lacunar stroke

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Loss of consciousness

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Lumbar radiculopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Mental impairment

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Metabolic encephalopathy

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Migraine

0.06%

5/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Migraine with aura

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Monoparesis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Multiple sclerosis relapse

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Myelopathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Nerve compression

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Nerve root compression

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Nervous system disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Neurological symptom

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Neuromyopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Neuropathy peripheral

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Normal pressure hydrocephalus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Paraesthesia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Paraplegia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Parkinsonism

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Presyncope

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Quadriparesis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Quadriplegia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Radial nerve palsy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Radicular pain

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Radiculopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Sacral radiculopathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Sciatica

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Seizure

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Senile dementia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Spinal claudication

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Spinal cord compression

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Spondylitic myelopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Status epilepticus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Subarachnoid haemorrhage

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Syncope

0.24%

19/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.26%

21/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.39%

31/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Thalamic infarction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Toxic encephalopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Transient global amnesia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Transient ischaemic attack

0.27%

22/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.36%

29/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.35%

28/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Tremor

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Trigeminal neuralgia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Unresponsive to stimuli

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Nervous system disorders

Vascular encephalopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Pregnancy, puerperium and perinatal conditions

Abortion spontaneous

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Device breakage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Device connection issue

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Device dislocation

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Device failure

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Device loosening

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Device malfunction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Device material issue

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Lead dislodgement

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Product Issues

Stent malfunction

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Acute psychosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Alcohol withdrawal syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Anxiety

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Bipolar I disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Bipolar disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Confusional state

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Delirium

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Depression

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Depression suicidal

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Disorientation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Drug abuse

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Dysphoria

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Hallucination, auditory

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Hypomania

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Major depression

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Mental status changes

0.12%

10/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.10%

8/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Panic attack

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Paranoia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Post-traumatic stress disorder

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Schizoaffective disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Schizophrenia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Substance abuse

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Suicidal ideation

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Psychiatric disorders

Suicide attempt

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Acute kidney injury

0.45%

36/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.49%

39/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.39%

31/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Acute prerenal failure

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Bladder outlet obstruction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Bladder prolapse

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Bladder spasm

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Calculus bladder

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Calculus urethral

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Calculus urinary

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Chronic kidney disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Cystitis haemorrhagic

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Dysuria

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Haematuria

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Hydronephrosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Hypertensive nephropathy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Incontinence

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Nephrolithiasis

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Nephropathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Nephrotic syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Renal artery stenosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Renal mass

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Stag horn calculus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Stress urinary incontinence

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Tubulointerstitial nephritis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Ureterolithiasis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Urethral stenosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Urinary incontinence

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Urinary retention

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Renal and urinary disorders

Urine flow decreased

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Adnexa uteri mass

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Atrophic vulvovaginitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Benign prostatic hyperplasia

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Breast disorder

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Breast mass

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Colpocele

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Cystocele

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Dysfunctional uterine bleeding

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Endometrial hyperplasia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Erectile dysfunction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Female genital tract fistula

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Menorrhagia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Metrorrhagia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Ovarian cyst

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Ovarian mass

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Pelvic adhesions

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Pelvic floor muscle weakness

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Pelvic prolapse

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Postmenopausal haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Prostatic obstruction

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Prostatitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Prostatomegaly

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Rectocele

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Spermatocele

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Uterine haemorrhage

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Uterine prolapse

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Uterovaginal prolapse

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Vaginal haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Reproductive system and breast disorders

Vaginal prolapse

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Acute respiratory distress syndrome

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Asphyxia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Aspiration

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Asthma

0.11%

9/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.16%

13/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Asthma-chronic obstructive pulmonary disease overlap syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Asthmatic crisis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Atelectasis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Bronchial hyperreactivity

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Bronchiectasis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Bronchitis chronic

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Bronchospasm

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Choking

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease

0.36%

29/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.38%

30/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.39%

31/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Cough

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Dyspnoea

0.20%

16/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.30%

24/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.30%

24/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Dyspnoea paroxysmal nocturnal

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Emphysema

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Eosinophilic pneumonia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Epistaxis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Haemoptysis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Hydrothorax

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Hypercapnia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Hypoventilation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Hypoxia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Idiopathic pulmonary fibrosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Laryngeal stenosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Lung consolidation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Lung infiltration

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Mediastinal mass

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Nasal congestion

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Nasal polyps

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Nasal septum deviation

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Obstructive airways disorder

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pickwickian syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pleural effusion

0.07%

6/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.08%

6/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pleurisy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pneumonitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pneumothorax

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pulmonary arterial hypertension

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism

0.22%

18/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.26%

21/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pulmonary fibrosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pulmonary hypertension

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pulmonary mass

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Pulmonary thrombosis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Respiratory arrest

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Respiratory disorder

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Respiratory distress

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Respiratory failure

0.10%

8/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.18%

14/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.13%

10/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Sleep apnoea syndrome

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Status asthmaticus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Tachypnoea

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Tracheal stenosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Respiratory, thoracic and mediastinal disorders

Vocal cord inflammation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Angioedema

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Dermal cyst

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Dermatitis bullous

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Diabetic foot

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Diabetic ulcer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Drug eruption

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Erythema multiforme

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Erythema nodosum

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Hyperhidrosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Hypersensitivity vasculitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Leukoplakia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Melanocytic hyperplasia

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Panniculitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Pruritus

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Rash

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Rash vesicular

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Skin ulcer

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Stasis dermatitis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Swelling face

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Skin and subcutaneous tissue disorders

Urticaria

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Social circumstances

Activities of daily living impaired

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Social circumstances

Immobile

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Social circumstances

Physical assault

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Bladder operation

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Cardiac pacemaker replacement

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Colporrhaphy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Coronary arterial stent insertion

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Coronary revascularisation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Cystocele repair

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Gastric banding

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Hernia repair

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Hip arthroplasty

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Hysterectomy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Inguinal hernia repair

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Joint fluid drainage

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Knee arthroplasty

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Ligament operation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Medical device removal

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Oophorectomy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Parovarian cystectomy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Renal artery stent placement

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Renal stone removal

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Shoulder arthroplasty

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Shoulder operation

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Spinal decompression

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Spinal fusion surgery

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Spinal operation

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Tenoplasty

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Thyroidectomy

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Vascular operation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Wound drainage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Accelerated hypertension

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Aneurysm

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Angiopathy

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Aortic aneurysm

0.12%

10/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Aortic aneurysm rupture

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Aortic arteriosclerosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Aortic calcification

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Aortic dilatation

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Aortic dissection

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Aortic stenosis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Arterial occlusive disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Arteriosclerosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Arteriovenous fistula

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Bleeding varicose vein

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Blue toe syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Deep vein thrombosis

0.15%

12/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.14%

11/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.15%

12/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Extravasation blood

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Extremity necrosis

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Haematoma

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Hypertension

0.22%

18/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.44%

35/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.26%

21/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Hypertensive crisis

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.09%

7/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.18%

14/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Hypertensive emergency

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Hypotension

0.09%

7/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.16%

13/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.11%

9/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Hypovolaemic shock

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Intermittent claudication

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Internal haemorrhage

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Ischaemia

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Labile hypertension

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Leriche syndrome

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Lymphoedema

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Malignant hypertension

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Orthostatic hypotension

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Arterial thrombosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Penetrating aortic ulcer

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Peripheral arterial occlusive disease

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.05%

4/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Peripheral artery aneurysm

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Peripheral artery occlusion

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Peripheral artery stenosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Peripheral artery thrombosis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Peripheral ischaemia

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Peripheral vascular disorder

0.05%

4/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.04%

3/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.06%

5/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Peripheral venous disease

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Phlebitis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Shock

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Subclavian vein thrombosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Systolic hypertension

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Temporal arteritis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Thrombophlebitis

0.02%

2/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Thrombophlebitis superficial

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Thrombosis

0.04%

3/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Varicose vein

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Vascular stenosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Venous thrombosis

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.03%

2/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Venous thrombosis limb

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Bradycardia and atrial flutter with hospitalization cardiorespiratory arrest and ischemia dilated

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Cardiac disorders

Cardiomyopathy and non-ST elevation MI and atherosclerosis

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Vascular disorders

Femoral popliteal occlusive disease

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Large granular lymphocyte

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Left hip surgical error

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic hepatic adenocarcinoma

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastatic tumor possibly from squamous cell lung cancer and metastatic tumor cerebral tumor

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

MRSA

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Musculoskeletal and connective tissue disorders

Osteoarthritis with tibial component loosening

0.00%

0/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.01%

1/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Infections and infestations

Pyelonephritis with sepsis NFI

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Surgical and medical procedures

Worsening osteoarthritis right hip replacement

0.01%

1/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

0.00%

0/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.

Trial Outcomes & Findings for Prospective Randomized Evaluation Of Celecoxib Integrated Safety Vs Ibuprofen Or Naproxen (NCT NCT00346216)

Results Overview

Participant Flow

Participant milestones

Reasons for withdrawal

Baseline Characteristics

Baseline characteristics by cohort

PRIMARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

Adverse Events

Celecoxib

Ibuprofen

Naproxen

Serious adverse events

Other adverse events

Additional Information

Pfizer Clinical Trials.gov Call Center

Results disclosure agreements

Measure	Celecoxib n=8072 Participants Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily	Ibuprofen n=8040 Participants Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily	Naproxen n=7969 Participants Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon1 (ITT) N=7382, 7379, 7325	-8.2 Number of participants Standard Deviation 24.69	-9.0 Number of participants Standard Deviation 25.69	-9.9 Number of participants Standard Deviation 25.53
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon36 MITT N=3691, 3623, 3635	-10.2 Number of participants Standard Deviation 29.61	-10.7 Number of participants Standard Deviation 29.62	-11.6 Number of participants Standard Deviation 29.80
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon42 MITT N=3468, 3404, 3438	-11.4 Number of participants Standard Deviation 29.78	-11.1 Number of participants Standard Deviation 30.14	-12.1 Number of participants Standard Deviation 30.27
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Baseline (ITT) N= 8014, 8001, 7928	54.0 Number of participants Standard Deviation 23.53	54.1 Number of participants Standard Deviation 23.58	54.1 Number of participants Standard Deviation 24.04
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon2 (ITT) N=7180, 7090, 7149	-10.5 Number of participants Standard Deviation 26.39	-10.6 Number of participants Standard Deviation 26.92	-11.1 Number of participants Standard Deviation 26.83
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon4 (ITT) N=6777, 6696, 6740	-11.4 Number of participants Standard Deviation 27.70	-11.7 Number of participants Standard Deviation 28.10	-12.3 Number of participants Standard Deviation 27.80
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon8 (ITT) N=6230, 6137, 6159	-11.7 Number of participants Standard Deviation 28.92	-12.1 Number of participants Standard Deviation 28.97	-12.1 Number of participants Standard Deviation 28.83
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon12 (ITT) N=5792, 5696, 5846	-11.0 Number of participants Standard Deviation 29.15	-11.6 Number of participants Standard Deviation 29.29	-11.9 Number of participants Standard Deviation 29.30
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon18 (ITT) N=5310, 5181. 5246	-11.3 Number of participants Standard Deviation 29.11	-11.3 Number of participants Standard Deviation 29.10	-11.7 Number of participants Standard Deviation 29.33
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon24 (ITT) N=4818, 4776, 4785	-11.3 Number of participants Standard Deviation 29.44	-11.5 Number of participants Standard Deviation 28.98	-11.4 Number of participants Standard Deviation 29.27
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon30 (ITT) N=4140, 4069, 4086	-10.5 Number of participants Standard Deviation 29.81	-11.2 Number of participants Standard Deviation 29.71	-11.3 Number of participants Standard Deviation 29.71
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon36 (ITT) N=3692, 3627, 3635	-10.1 Number of participants Standard Deviation 29.61	-10.7 Number of participants Standard Deviation 29.62	-11.6 Number of participants Standard Deviation 29.80
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon42 (ITT) N=3469, 3406, 3439	-11.4 Number of participants Standard Deviation 29.78	-11.1 Number of participants Standard Deviation 30.14	-12.1 Number of participants Standard Deviation 30.27
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Baseline (MITT) N=7974, 7954, 7894	54.0 Number of participants Standard Deviation 23.53	54.1 Number of participants Standard Deviation 23.58	54.1 Number of participants Standard Deviation 24.02
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon1 MITT N=7372, 7367, 7321	-8.2 Number of participants Standard Deviation 24.69	-9.0 Number of participants Standard Deviation 25.67	-9.9 Number of participants Standard Deviation 25.53
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon2 MITT N=7170, 7078, 7142	-10.5 Number of participants Standard Deviation 26.38	-10.6 Number of participants Standard Deviation 26.92	-11.1 Number of participants Standard Deviation 26.84
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon4 MITT N=6772, 6686, 6732	-11.4 Number of participants Standard Deviation 27.70	-11.7 Number of participants Standard Deviation 28.10	-12.3 Number of participants Standard Deviation 27.81
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon8 MITT N=6224, 6128, 6155	-11.7 Number of participants Standard Deviation 28.93	-12.1 Number of participants Standard Deviation 28.97	-12.1 Number of participants Standard Deviation 28.84
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon12 MITT N=5787, 5689, 5844	-11.0 Number of participants Standard Deviation 29.16	-11.6 Number of participants Standard Deviation 29.30	-11.9 Number of participants Standard Deviation 29.30
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon18 MITT N=5305, 5175, 5242	-11.3 Number of participants Standard Deviation 29.11	-11.3 Number of participants Standard Deviation 29.12	-11.7 Number of participants Standard Deviation 29.33
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon24 MITT N=4815, 4769, 4782	-11.4 Number of participants Standard Deviation 29.44	-11.5 Number of participants Standard Deviation 29.00	-11.3 Number of participants Standard Deviation 29.26
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) Change-Baseline to Mon30 MITT N=4139, 4067, 4085	-10.5 Number of participants Standard Deviation 29.81	-11.2 Number of participants Standard Deviation 29.71	-11.3 Number of participants Standard Deviation 29.70

Measure	Celecoxib n=8030 participants at risk Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily	Ibuprofen n=7992 participants at risk Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily	Naproxen n=7933 participants at risk Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily.
Blood and lymphatic system disorders Anaemia	2.6% 207/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.1% 405/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	3.9% 310/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Gastrointestinal disorders Constipation	3.4% 274/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	4.3% 344/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.1% 408/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Gastrointestinal disorders Diarrhoea	8.0% 641/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	6.7% 538/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	7.1% 566/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Gastrointestinal disorders Dyspepsia	4.9% 393/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.3% 424/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.5% 436/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.0% 401/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.1% 404/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	4.9% 387/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Gastrointestinal disorders Nausea	5.3% 425/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	6.0% 482/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	6.3% 502/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Infections and infestations Bronchitis	5.8% 465/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.9% 471/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.4% 427/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Infections and infestations Sinusitis	4.6% 373/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.3% 421/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	4.7% 375/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Infections and infestations Upper respiratory tract infection	7.3% 584/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	7.4% 595/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	7.1% 560/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Infections and infestations Urinary tract infection	5.2% 416/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.7% 452/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.2% 414/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Musculoskeletal and connective tissue disorders Arthralgia	9.5% 764/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	8.2% 659/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	9.6% 764/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Musculoskeletal and connective tissue disorders Back pain	6.7% 542/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	6.5% 516/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	6.9% 547/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Musculoskeletal and connective tissue disorders Osteoarthritis	11.9% 958/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	10.7% 859/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	11.1% 880/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 455/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.3% 422/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.3% 422/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Nervous system disorders Headache	4.5% 361/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	5.1% 409/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	4.6% 365/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.
Vascular disorders Hypertension	9.5% 762/8030 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	12.6% 1008/7992 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.	10.8% 855/7933 • Adverse events were reported from the signing of the informed consent throughout the entire study period (42 months) and including 30 calendar days after the last administration of the investigational product.